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ACS Chem Biol. 2006 Oct 24;1(9):594-600.

Conjugating berberine to a multidrug efflux pump inhibitor creates an effective antimicrobial.

Author information

1
Department of Biology and Antimicrobial Discovery Center, Northeastern University, Boston, Massachusetts 02115, USA.

Abstract

In bacteria, multidrug-resistance pumps (MDRs) confer resistance to chemically unrelated amphipathic toxins. A major challenge in developing efficacious antibiotics is identifying antimicrobial compounds that are not rapidly pumped out of bacterial cells. The plant antimicrobial berberine, the active component of the medicinal plants echinacea and golden seal, is a cation that is readily extruded by bacterial MDRs, thereby rendering it relatively ineffective as a therapeutic agent. However, inhibition of MDR efflux causes a substantial increase in berberine antimicrobial activity, suggesting that berberine and potentially many other compounds could be more efficacious if an effective MDR pump inhibitor could be identified. Here we show that covalently linking berberine to INF 55 , an inhibitor of Major Facilitator MDRs, results in a highly effective antimicrobial that readily accumulates in bacteria. The hybrid molecule showed good efficacy in a Caenorhabditis elegans model of enterococcal infection, curing worms of the pathogen.

PMID:
17168555
DOI:
10.1021/cb600238x
[Indexed for MEDLINE]
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